■NET,一种独特的中性粒细胞免疫机制,在抵御微生物入侵方面至关重要。了解白色念珠菌和金黄色葡萄球菌共同感染的机制,这通常会导致更高的死亡率和更差的预后,对于研究感染进展至关重要。
■在我们的研究中,我们建立了皮下感染的小鼠模型,以表征共同感染引起的炎症。通过纯化和提取NET与微生物相互作用,我们深入研究了它们与各种微生物物种相互作用的差异。此外,我们通过中性粒细胞与单一微生物或混合微生物的相互作用,研究了中性粒细胞产生NETs的差异.此外,我们使用转录组学分析了共感染期间的基因表达差异.
■体内,白色念珠菌感染倾向于聚集,而金黄色葡萄球菌感染更分散。在共感染的情况下,金黄色葡萄球菌粘附并包裹白色念珠菌。NET表现出对白色念珠菌的强杀伤能力,但对金黄色葡萄球菌的效力较弱。当NET与混合微生物相互作用时,它们优先靶向并杀死金黄色葡萄球菌的外层。在早期阶段,中性粒细胞主要依靠吞噬作用来杀死金黄色葡萄球菌,但是随着细菌的积累,它们刺激中性粒细胞产生NET。有趣的是,在中性粒细胞的存在下,金黄色葡萄球菌促进白色念珠菌的增殖和菌丝生长。
■我们的研究表明,与单一微生物感染相比,共感染的进展存在重大差异,从而为NETs作为共同感染治疗的潜在治疗靶点提供了科学依据。
UNASSIGNED: NETs, a unique neutrophil immune mechanism, are vital in defending against microbial invasions. Understanding the mechanisms of co-infection by Candida albicans and Staphylococcus aureus, which often leads to higher mortality and poorer prognosis, is crucial for studying infection progression.
UNASSIGNED: In our study, we established a mouse model of subcutaneous infection to characterize the inflammation induced by co-infection. By purifying and extracting NETs to interact with microorganisms, we delve into the differences in their interactions with various microbial species. Additionally, we investigated the differences in NETs production by neutrophils in response to single or mixed microorganisms through the interaction between neutrophils and these microorganisms. Furthermore, we analyzed the gene expression differences during co-infection using transcriptomics.
UNASSIGNED: In vivo, C. albicans infections tend to aggregate, while S. aureus infections are more diffuse. In cases of co-infection, S. aureus adheres to and wraps C. albicans. NETs exhibit strong killing capability against C. albicans but weaker efficacy against S. aureus. When NETs interact with mixed microorganisms, they preferentially target and kill the outer layer of S. aureus. In the early stages, neutrophils primarily rely on phagocytosis to kill S. aureus, but as the bacteria accumulate, they stimulate neutrophils to produce NETs. Interestingly, in the presence of neutrophils, S. aureus promotes the proliferation and hyphal growth of C. albicans.
UNASSIGNED: Our research has showed substantial differences in the progression of co-infections compared to single-microbial infections, thereby providing scientific evidence for NETs as potential therapeutic targets in the treatment of co-infections.